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Biomedical subjects

K R Krishnan

Publications and source records attributed to K R Krishnan.

At least 181 records · Page 10Linked to original sources

Cerebral white matter disease in late-onset paranoid psychosis.

We examined magnetic resonance (MR) scans of the heads of 8 patients with late onset psychosis and 8 aged controls. Although some patients had mild cognitive impairment, none had depression or a history or examination suggesting focal brain disease. Thus, all patients met DSM-III-R criteria for late-onset schizophrenia. All 8 patients showed significant leukoencephalopathy or vascular pathology on MR imaging, and temporoparietal and occipital lesions were especially prominent. Little such pathology was evident on control scans. We suggest that focal brain disease of vascular origin may be associated with late-onset psychosis, and that MR scanning of such cases may provide important clues to pathogenesis.

Aged↗

A brain magnetic resonance imaging study of pituitary gland morphology in anorexia nervosa and bulimia.

Magnetic resonance imaging (MRI) of the brain was used to examine the morphology and dimensions of the pituitary gland in 18 patients with eating disorders (8 anorectics and 10 bulimics), in comparison with 13 healthy volunteers. None of the 18 patients with anorexia or bulimia had any radiological evidence suggestive of pituitary macroadenoma, cyst, or empty sella. Measurements revealed that the anorectics and bulimics had smaller pituitary gland cross-sectional areas (p less than 0.05) and smaller pituitary gland heights, compared with healthy controls. These preliminary findings in anorectics and bulimics are suggestive of pituitary atrophy secondary to nutritional or endocrine alterations, rather than a primary pituitary pathology.

Adolescent↗

Nocturnal and early morning secretion of ACTH and cortisol in humans.

It is well established that the adrenocorticotropic hormone (ACTH) stimulates the synthesis and release of cortisol from the adrenal cortex, but the role of ACTH in the physiological regulation of basal cortisol secretion has received surprisingly little study. The authors studied the nocturnal and early morning secretory pulses of cortisol and ACTH in normal subjects. A pulse detection algorithm was developed. The relationship between ACTH and cortisol pulses in terms of temporal and proportional relationship is described. Pulse concomitance for ACTH with cortisol was 47% and for cortisol with ACTH pulses it was 60%. The first description of the relationship between concomitant ACTH and cortisol pulse magnitudes in humans is presented. A highly significant linear relationship between the magnitudes of ACTH and cortisol pulses is shown. Putative reasons for dissociated pulses and the potential implication of these findings are discussed.

Adrenocorticotropic Hormone↗

Plasma dexamethasone concentrations and the dexamethasone suppression test.

Altered bioavailability or altered pharmacokinetics of dexamethasone (dex) may contribute to a positive Dexamethasone Suppression Test (DST) in psychiatric patients. We measured plasma dex and plasma cortisol concentrations in 32 patients with primary major depressive disorder (MDD), 14 patients with other psychiatric disorders, and 16 normal controls. Cortisol was measured by the competitive protein binding (CPB) assay and dex by RIA (IgG Corp.). Additionally, cortisol was measured by a fluorescent polarization immunoassay (FPIA) available on the Abbott TDx analyzer in an attempt to validate this method for use in the DST. The agreement between FPIA and CPB cortisol results was excellent. Depressed nonsuppressors, by definition, had significantly higher mean plasma cortisol concentrations than depressed suppressors, psychiatric controls, and normal volunteers at 8:00 AM, 3:00 PM, and 10:00 PM postdex. When DST nonsuppressors and suppressors were compared regardless of diagnostic group, plasma dex concentrations were significantly lower (p less than 0.01) in the DST nonsuppressors. There was a significant negative correlation between plasma cortisol levels and plasma dex levels across all subjects at 8:00 AM (r = -0.365, n = 44, p less than 0.05). When the subjects were sorted by diagnostic category, there was a strong, but not statistically significant, trend toward lower plasma dex concentrations in the melancholic nonsuppressors versus the melancholic suppressors and between the psychiatric control non-suppressors and the corresponding suppressor group. These relationships disappeared when we restricted our analyses to an empirically derived middle range of plasma dex concentrations within which the DST results were considered to be valid. We conclude that bioavailability or pharmacokinetics of dex may significantly contribute to DST results. Further investigation is needed to determine whether or not the quantification of dex and its metabolites and their determination at which specific timepoints during the DST will enhance the predictive or interpretive value of the DST in psychiatric patients.

Adult↗

Elevated plasma concentrations of alpha 1-acid glycoprotein, a putative endogenous inhibitor of the tritiated imipramine binding site, in depressed patients.

The plasma concentration of alpha 1-acid glycoprotein, a putative endogenous inhibitor of the site labeled by tritiated imipramine, was measured by a radial immunodiffusion assay in 36 normal human volunteers and 51 drug-free patients who fulfilled DSM-III criteria for major depression. The depressed patients exhibited a significant elevation in the plasma concentration (+/- SEM) of alpha 1-acid glycoprotein (79.6 +/- 4 mg/dL) when compared with the age- and sex-matched controls (61.7 +/- 3 mg/dL). Fourteen of the 51 patients with major depression had plasma alpha 1-acid glycoprotein concentrations that were higher than the highest values of the normal controls. There was no relationship between plasma alpha 1-acid glycoprotein concentrations and sex or affinity of platelet tritiated imipramine binding of either the normal volunteers or the depressed patients. In the depressed patients, there was a significant positive correlation between plasma concentrations of alpha 1-acid glycoprotein and postdexamethasone plasma cortisol concentrations, and two measures of depression severity, the Montgomery-Asberg Rating Scale for Depression and the Center for Epidemiologic Studies-Depression Scale, and a significant negative correlation with age. These data provide the first evidence of alterations of an endogenous inhibitor of the tritiated imipramine binding site/serotonin transporter in depressed patients.

Adult↗

In vivo stereological assessment of caudate volume in man: effect of normal aging.

Using intermediate weighted magnetic resonance imaging (MRI) and a systematic sampling stereological method in 39 normal volunteers aged 24-79 years old, we demonstrated a marked age-associated decline in caudate nuclei volume (r = -0.69, p less than 0.0001). The mean absolute volume of the caudate nuclei in this study (9.4 cm3) was almost identical to that reported in a previous autopsy study and further confirms the validity of this stereological technique for use with MR images. This technique will provide a method for measuring the caudate and other nuclei in vivo, from brain images and, as such, a research tool to correlate age-associated changes in cognitive, sensory and motor function with caudate nucleus volume and other brain regions.

Adult↗

Antibody coated bacteria in urine of patients with recent spinal injury.

Twenty patients with an acute spinal injury were prospectively studied to assess the clinical importance of antibody coated bacteria (ACB) in the urine and the association among the different bacterial species with a positive antibody coated bacteria test. Clinical urinary tract infection was associated with a positive ACB test on 45% of occasions. Three hundred and ninety nine urine samples containing 541 bacterial isolates were assessed for the presence of ACB; 13% were found to be positive and 87% negative for ACB; 67% of urines contained a single bacterial isolate. Pseudomonas aeruginosa was most commonly associated with clinical urinary tract infection, found in 25% of episodes, followed by Proteus mirabilis (17.5%), Klebsiella sp (12.5%), and Proteus morganii (10%). Providencia stuartii, however, was most commonly associated with a positive ACB test (found in 17%). Other bacteria associated with a positive ACB test included Klebsiella sp (14%), Acinetobacter sp (12.5%), Pseudomonas aeruginosa (12%), Citrobacter sp (11.5%). A positive ACB test is not to be expected from a patient with spinal injury who has a catheter in place, and the test may provide a useful guide to identify those patients with an invasive infection. It is doubtful that a decision to treat or not treat bacteriuria could rest on the identification of the bacterial species alone.

Acute Disease↗

Differential diagnosis and pathophysiology of Cushing's syndrome and primary affective disorder.

Most patients with major depression have increased 24-hour urinary free cortisol and cortisol nonsuppression after dexamethasone administration, which are cornerstones of a diagnosis of Cushing's syndrome. Similarly, Cushing's syndrome patients often suffer from major psychiatric syndromes, most often depression. These similarities between the two conditions sometimes make it difficult to differentiate them and have led some investigators to suggest they are two points on a spectrum of endocrinologic dysfunction. This article reviews the literature comparing Cushing's syndrome and primary affective disorder and presents two cases that illustrate just how closely these diseases may resemble one another.

Adrenocorticotropic Hormone↗

In vivo assessment of pituitary gland volume with magnetic resonance imaging: the effect of age.

We used sagittal and coronal T1 weighted magnetic resonance images, at 1.5 Tesla, to measure the height, width, length, and cross-sectional area and to generate two estimates of pituitary gland volume in 35 normal volunteers aged 26-79 yr (19 females and 16 males). Subjects over 50 yr of age had significantly smaller pituitary gland height (P = 0.03), area (P = 0.04), and volume (P = 0.04) than those under 50 yr (by two-tailed t test). Overall, age was negatively correlated with pituitary volume (V1: r = -0.51; P = 0.003; V2: r = -0.47; P = 0.008), area (r = -0.43; P = 0.009), and height (r = -0.46; P = 0.005), but not with pituitary length or width. There were no statistically significant differences in pituitary size between men and women (by two-tailed t test). These findings suggest that pituitary gland height provides a good single measure for the assessment of pituitary gland size and that age must be controlled for in studies of pituitary gland size.

Adult↗

Pharmacologic management of the symptoms of dementia.

Many patients with dementia have symptoms of depression and agitation in addition to the underlying cognitive impairment. These symptoms can be management problems for both the physician and the caregiver. In many cases, however, pharmacologic intervention is helpful. Even in dementia, depressive symptoms usually respond to antidepressant therapy. Neuroleptic medications are the drugs most commonly used to manage behavioral symptoms, such as agitation, suspiciousness, emotional lability, hostility and sleeplessness. A few studies have shown that ergoloid mesylates (Hydergine) can modestly improve cognitive function. Some experimental drugs also show promise in partially reversing the symptoms of intellectual decline.

Aged↗

Psychiatric syncope: a new look at an old disease.

Psychiatric disorders in patients with unexplained syncope or presyncope have received little attention in the recent medical literature. Seventy-two patients with unexplained syncope and presyncope referred to the Duke Syncope Clinic received a standardized evaluation. Symptoms appeared to be explained by a psychiatric diagnosis in 17 (24%) patients (panic disorder in 13%, and major depression in 11%). These patients were younger than other patients with syncope and presyncope (p less than .001) and had more disability due to their syncope and presyncope (p less than .01). They also had more frequent episodes of syncope (p less than .005) and more symptoms as a part of their prodrome (p less than .0001). Treatment aimed at the psychiatric diagnosis resulted in a remission from syncopal or presyncopal symptoms in 90% of patients who complied with therapy. The authors conclude that psychiatric disorders are common in patients with syncope and presyncope, that certain characteristics of the patient and prodrome may alert physicians to a psychiatric diagnosis, and that directed treatment may result in relief from symptoms.

Anxiety Disorders↗

Reduced inhibitory effect of imipramine on radiolabeled serotonin uptake into platelets in geriatric depression.

Tritiated imipramine binding, uptake of radiolabeled serotonin, and inhibition of uptake by imipramine in vitro were studied in platelets obtained from four groups of subjects: (1) normal controls 50 years of age or younger, (2) patients with major depression 50 years of age or younger, (3) normal controls 60 years of age or older, and (4) patients with major depression 60 years of age or older. Depression in both age groups was associated with a substantial decrease in the number of [3H]imipramine binding sites; the elderly depressed patients exhibited a small but significant (p less than 0.05) reduction in platelet [3H]serotonin uptake. However, the inhibition of serotonin uptake into platelets by imipramine was markedly reduced only in the elderly depressed patients. This reduced sensitivity to imipramine may explain the reduced responsiveness of patients with geriatric depression to the therapeutic effects of imipramine and other tricyclic antidepressants.

Adult↗

Growth hormone response to growth hormone releasing factor in Alzheimer's disease.

Because of the well-established reduction in the concentration of somatostatin in several brain areas of patients with histologically verified Alzheimer's disease, we sought to determine if growth hormone (GH) secretion is altered in Alzheimer's disease. In order to study this, we assessed the GH response to growth hormone releasing factor (GRF) in 8 patients with Alzheimer's disease and 8 age-matched controls. Although there was no difference between the magnitude of the GRF-induced GH response (delta max GH response or area under the curve) between the Alzheimer's disease patients and the controls, the Alzheimer's patients exhibited a delayed GH response to GRF.

Aged↗

Radiologic correlates of antidepressant-induced delirium: the possible significance of basal-ganglia lesions.

Antidepressant-induced delirium in five of 60 (8%) patients over the age of 45 is reported. In each case, delirium developed within two weeks of beginning the antidepressant and appeared to be completely reversible once the medication was discontinued. Brain magnetic resonance imaging revealed basal-ganglia lesions in each patient who developed delirium. This finding indicates that patients with basal-ganglia lesions may be more vulnerable to antidepressant-induced delirium and is consistent with recent data from the neurologic and psychiatric literature that implicate the basal ganglia in the development of other types of delirium.

Aged↗